A versatile nano-transformer for efficient localization-specific imaging and synergistic therapy of bladder cancer

A stepwise morphologic transformation is highly desirable but rarely reported for promoting drug penetration at tumor sites via reducing transport barriers. Herein, an adhesive multifunctional nano-transformer (CTMF NPs) with cascading structural transformation was constructed, which afforded tumor microenvironment (TME)-activatable zero-background 19 F-magnetic resonance imaging and ratiometric photoacoustic imaging-guided synergistic tumor therapy. CTMF NPs were synthesized via a one-pot encapsulation and dynamic coordination strategy, where copper sulfide nanoparticles (CuS NPs, photothermal agent) were co-encapsulated with perfluoro-15-crown-5-ether (PFCE, 19 F MRI agent) by the dopamine grafted amphiphilic polymer, followed by coating with metal (Mn 2+ )-polyphenol shell ( 19 F signal quencher and therapeutic agent). Benefiting from polyphenol enhanced cell adherence as well as in situ generated reactive quinone , the CTMF NPs attached to tumor sites and exhibited efficient internalization under TME promoted decomposition and oxidation . Moreover, these nano-platforms were further decomposed under laser irradiation , which amplified cellular oxidative stress , leading to mitochondrial structural damage and dysfunction, as well as facilitating cuproptosis by interfering with the lipoylated tricarboxylic acid cycle . Cell apoptosis subsequently resulted in significant immunogenic cell death and afforded a versatile nano-transformer for precise imaging-guided bladder cancer therapy.